Penyakit disebabkan oleh Cadmium

Introduction

Itai-itai disease was found in the cadmium(Cd) polluted Jinzu River basin in Toyama Prefecture, and has been generally recognized since the 1950's by the effort of inhabitants and Dr. Hagino who was a general practitioner with a private clinic in the polluted area.

Itai-itai disease was officially recognized in 1968 as the first disease induced by environmental pollution in Japan after legal proceedings. The basis of the court decision is simply but clearly shown in "The view of the Ministry of Health and Welfare" which consisted of 7 articles and was announced on 8th May, 1968. Especially, the basis that concluded the cause of the disease to be Cd pollution was epidemiological evidence that only cadmium can explain the limited development of itai-itai disease in a specific area around parts of the Jinzu River.

Epidemiology

The degree of Cd pollution in different parts of the endemic area determined by the analyzed Cd concentration of the soil in the paddy fields was shown in Fig.1. In Fig.2, the frequency of the disease is illustrated by the percentage of women over 50 years of age having or suspected of having the disease. The striking correlation between the prevalence of itai-itai disease and degree of Cd pollution was found even within the endemic area.

Itai-itai disease is considered to be a type of acquired Fanconi Syndrome characterized by renal tubular dysfunction and osteomalacia and has been found among middle aged and elderly women with relatively frequent pregnancy, living in the cadmium polluted area for more than 30 years.

A markedly increased excretion of urinary molecular weight proteins such as (β2-microglobulin, glucose, protein and amino acids is found in itai-itai disease patients, and these findings are indices of renal tubular dysfunction. Low level of %TRP and metabolic acidosis with high serum Cl are also found. In severe cases increased serum creatinine that shows impairment of renal glomerular function is recognized.

Pathologically, renal damage of itai-itai disease is characterized by atrophic kidney as shown in Fig.3. The weight of the kidney is usually decreased to around 60g, and to 30g's in cases with non-specific inflammation or atherosclerotic change. Microscopically, tubulopathy is found as shown in Fig.4.

Another specific finding of itai-itai disease is osteomalacia. The remodeling layer called "Looser zone" shown in Fig.5 and Fig.6 is characteristic. Looser zone is often found in femur, pelvis and ribs. Osteoporosis is also associated with X-ray findings such as unclear trabecular pattern and cortial bone thinning noted.

Pathologically, increased osteoid tissue is characteristic of osteomalacia, as shown in Fig.7

Prognosis

Bone damage tends to become refractory in some cases, but to remit by treatment such as vitamin D2 or activated Vitamin D3 treatment as a whole.

However, renal damage progresses to advanced renal failure(Fig.8), and some cases of uremia need hemodialysis. Anemia also develops in proportion to the degree of renal failure.

Survival rate of itai-itai disease patients is significantly lower than that of controls (Fig.9), and especially life prognosis of cases with severe renal damage is unfavorable.

Renal tubular dysfunction is well known as an adverse health effect of environmental cadmium exposure, and is characterized by the increased urinary excretion of low molecular weight proteins such as beta2-microglobulin(β2-MG).

Increased urinary excretion of total protein, glucose and amino acids is also found in the inhabitants living in cadmium polluted areas. Low %TRP(percentage of tubular reabsorption of phosphorus) and metabolic acidosis are found in moderate and severe cases.

Most severe renal damage developing in itai-itai disease patients is accompanied with renal glomerular dysfunction progressing to renal failure.

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The following map shows the location of cadmium polluted areas in Japan, and the number of subjects, positive rate of urinary cadmium and positive rate of urinary protein and glucose of inhabitants living in each area. Urinary cadmium is an index of cadmium exposure. Although positive rate of urinary protein and glucose is less sensitive than β2-MG for screening of renal tubular dysfunction, you can see that Jinzu River basin in Toyama where itai-itai disease has been found, is the most heavily polluted and affected area by cadmium in Japan.